JP5027891B2 - Analysis method - Google Patents

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JP5027891B2
JP5027891B2 JP2010001201A JP2010001201A JP5027891B2 JP 5027891 B2 JP5027891 B2 JP 5027891B2 JP 2010001201 A JP2010001201 A JP 2010001201A JP 2010001201 A JP2010001201 A JP 2010001201A JP 5027891 B2 JP5027891 B2 JP 5027891B2
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tube
factor
sample
standard
nmr
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JP2011141160A (en
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治男 島田
桂子 大竹
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Shiseido Co Ltd
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Shiseido Co Ltd
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Priority to JP2010001201A priority Critical patent/JP5027891B2/en
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Priority to CN2010800608661A priority patent/CN102741700A/en
Priority to EP14162840.4A priority patent/EP2752677B1/en
Priority to KR1020127017133A priority patent/KR20120116953A/en
Priority to PCT/JP2010/073732 priority patent/WO2011083730A1/en
Priority to EP10842241.1A priority patent/EP2523010A4/en
Priority to US13/520,420 priority patent/US9335388B2/en
Priority to TW099147364A priority patent/TW201132969A/en
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本発明は、分析方法に関する。 The present invention relates to a minute析方method.

従来、試料を定量分析する方法としては、ＨＰＬＣ、ＧＣ等が知られているが、ＮＭＲも用いられているようになってきている。   Conventionally, HPLC, GC, and the like are known as methods for quantitative analysis of samples, but NMR is also being used.

特許文献１には、酸素−１７核を含有した化合物を定量する方法として、標準物質として、試料とは酸素−１７核の共鳴周波数が異なる物質を用い、標準物質と試料とを同時にＮＭＲ測定する方法が開示されている。また、同軸二重試料管を用いて、内管に試料、外管に標準物質を入れて測定する方法が開示されている。   In Patent Document 1, as a method for quantifying a compound containing oxygen-17 nuclei, a substance having a resonance frequency of oxygen-17 nuclei different from that of a sample is used as a standard substance, and the standard substance and the sample are simultaneously subjected to NMR measurement. A method is disclosed. Also disclosed is a method of measuring by using a coaxial double sample tube and putting a sample in the inner tube and a standard substance in the outer tube.

しかしながら、試料を入れ替える毎に、標準物質も入れ替えなければならないことに加え、揮発性の標準物質を用いて定量できないという問題がある。   However, every time the sample is replaced, the standard material must be replaced, and there is a problem in that it cannot be quantified using a volatile standard material.

特開２００４−２８６７１２号公報JP 2004-286712 A

本発明は、上記の従来技術が有する問題に鑑み、標準物質を入れ替えずに試料を入れ替えてＮＭＲを測定すると共に、揮発性の標準物質を用いても定量することが可能な分析方法を提供することを目的とする。 In view of the problem of the prior art described above has, provided with measuring the NMR interchanged sample without replacing the standard, the partial析方method which can quantify be used volatile standard The purpose is to do.

請求項１に記載の発明は、分析方法において、二重管構造を有し、一端が閉じている第一の管の中に一端が閉じている第二の管が入れられている状態で、該第一の管と該第二の管の間が溶閉されており、該溶閉されている第一の管と第二の管の間に、定量用標準物質が入れられているＮＭＲ試料管にファクター用標準物質が重溶媒中に溶解している溶液を入れる工程と、該ファクター用標準物質が重溶媒中に溶解している溶液が入れられたＮＭＲ試料管を用いて、前記ファクター用標準物質の１ＨＮＭＲスペクトルを測定することにより、ＮＭＲ試料管のファクターを求める工程と、該ファクターが求められたＮＭＲ試料管に化合物Ｘを含む試料を入れる工程と、該試料が入れられたＮＭＲ試料管を用いて、前記試料の １ ＨＮＭＲスペクトルを測定することにより、前記試料中の前記化合物Ｘの含有量を定量分析する工程を有し、前記ファクター用標準物質が重溶媒中に溶解している溶液中の前記ファクター用標準物質の濃度をＡ０［ｍｏｌ／Ｌ］、前記ファクター用標準物質の１ＨＮＭＲスペクトルにおける前記定量用標準物質の面積を１としたときの前記ファクター用標準物質の１Ｈ分の面積をＢ０、前記ＮＭＲ試料管のファクターをＦ［ｍｏｌ／Ｌ］、前記化合物Ｘの分子量をＭ、前記ＮＭＲ試料管に入れられた試料の濃度をＡ １ ［ｇ／Ｌ］、前記試料の １ ＨＮＭＲスペクトルにおける前記定量用標準物質の面積を１としたときの前記化合物Ｘの１Ｈ分の面積をＢ １ 、前記ＮＭＲ試料管に入れられた化合物Ｘの濃度をＣ １ ［ｇ／Ｌ］、前記試料中の前記化合物Ｘの含有量をＤ １ ［質量％］とすると、式
Ｆ＝Ａ０／Ｂ０
Ｃ １ ＝Ｂ １ ×Ｆ×Ｍ
Ｄ １ ＝（Ｃ １ ／Ａ １ ）×１００
を満たすことを特徴とする。
請求項２に記載の発明は、請求項１に記載の分析方法において、前記定量用標準物質は、マレイン酸、テトラメチルシラン、３−トリメチルシリルプロピオン酸、１，４−ジオキサン、１，４−ビス（トリメチルシリル）ベンゼン、ベンゼントリカルボン酸、ジメチルシラペンタンスルホン酸ナトリウム、トリアジン、フェナジン、リン酸、トリフルオロ酢酸、水、ベンゼン、クロロホルム、メタノール又はジメチルスルホキシドであることを特徴とする。
請求項３に記載の発明は、請求項１又は２に記載の分析方法において、前記ファクター用標準物質は、フタル酸水素カリウム、エタノール、リン酸、トリフルオロ酢酸、ジメチルシラペンタンスルホン酸ナトリウム、３−トリメチルシリルプロピオン酸ナトリウム又は水であることを特徴とする。

The invention according to claim 1 is the analysis method, wherein the second tube having one end is closed in the first tube having a double tube structure and one end is closed. An NMR sample in which the space between the first tube and the second tube is closed, and a standard substance for quantification is placed between the closed first tube and the second tube Using a NMR sample tube in which a solution in which the factor reference material is dissolved in a heavy solvent and an NMR sample tube in which the solution in which the factor standard material is dissolved in the heavy solvent are placed in the tube. by measuring the 1 HNMR spectrum of the standard, a step of determining the factor of the NMR sample tube, comprising the steps of placing the sample containing the compound X to the NMR sample tube in which the factor has been determined, NMR sample sample was placed with tubes, 1 HNMR spectrum of the sample By measuring comprises the step of quantitatively analyzing the content of the compound X in the sample, the concentration of said factor for standard solution in which the factors for a standard substance is dissolved in the heavy solvent A 0 [mol / L], where the area of the standard substance for quantification in the 1 H NMR spectrum of the standard substance for factor is 1, and the area of 1H of the standard substance for factor is B 0 , The factor is F [mol / L] , the molecular weight of the compound X is M, the concentration of the sample placed in the NMR sample tube is A 1 [g / L], and the standard substance for quantification in the 1 HNMR spectrum of the sample the area of 1H amount of the compound X when the area and 1 B 1, the concentration of compound X which is placed in the NMR sample tube C 1 [g / L], the compound X in the sample When a chromatic amounts to D 1 [wt%], the formula F = A 0 / B 0
C 1 = B 1 × F × M
D 1 = (C 1 / A 1 ) × 100
It is characterized by satisfying.
The invention according to claim 2 is the analysis method according to claim 1, wherein the standard substance for quantification is maleic acid, tetramethylsilane, 3-trimethylsilylpropionic acid, 1,4-dioxane, 1,4-bis. It is characterized by being (trimethylsilyl) benzene, benzenetricarboxylic acid, sodium dimethylsilaptansulfonate, triazine, phenazine, phosphoric acid, trifluoroacetic acid, water, benzene, chloroform, methanol or dimethylsulfoxide.
According to a third aspect of the present invention, in the analysis method according to the first or second aspect, the standard substance for factor is potassium hydrogen phthalate, ethanol, phosphoric acid, trifluoroacetic acid, sodium dimethylsilapentanesulfonate, -Sodium trimethylsilylpropionate or water.

本発明によれば、標準物質を入れ替えずに試料を入れ替えてＮＭＲを測定すると共に、揮発性の標準物質を用いても定量することが可能な分析方法を提供することができる。

According to the present invention, it can be provided with measuring the NMR interchanged sample without replacing the standard, the partial析方method which can quantify be used volatile standards.

本発明のＮＭＲ試料管の一例を示す図である。It is a figure which shows an example of the NMR sample tube of this invention. 実施例で得られた消毒液の１ＨＮＭＲスペクトルである。 1 is a 1 HNMR spectrum of a disinfectant solution obtained in Examples.

次に、本発明を実施するための形態を図面と共に説明する。   Next, the form for implementing this invention is demonstrated with drawing.

図１に、本発明のＮＭＲ試料管の一例を示す。ＮＭＲ試料管１０は、同軸の円筒二重管構造を有し、外管１１と内管１２の間が溶閉されており、外管１１と内管１２の間には、重溶媒に溶解した標準物質１３が入れられている。このため、ＮＭＲ試料管１０を用いると、標準物質１３を入れ替えずに試料を入れ替えてＮＭＲを測定すると共に、揮発性の標準物質を用いても定量することができる。   FIG. 1 shows an example of the NMR sample tube of the present invention. The NMR sample tube 10 has a coaxial cylindrical double tube structure, and the outer tube 11 and the inner tube 12 are sealed. The outer tube 11 and the inner tube 12 are dissolved in a heavy solvent. A standard substance 13 is contained. For this reason, when the NMR sample tube 10 is used, NMR can be measured by exchanging the sample without exchanging the standard substance 13, and quantification can be performed even if a volatile standard substance is used.

重溶媒としては、外部標準物質１３を溶解させることが可能であれば、特に限定されないが、重クロロホルム、重アセトニトリル、重アセトン、重ベンゼン、重シクロヘキサン、重水、重ジクロロベンゼン、重ジエチルエーテル、重ジメチルホルムアミド、重ジメチルスルホキシド、重ジオキサン、重酢酸エチル、重エタノール、重メタノール、重ニトロベンゼン、重ピリジン、重テトラクロロエタン、重トルエン、重トリフルオロ酢酸等が挙げられる。   The heavy solvent is not particularly limited as long as the external standard substance 13 can be dissolved. However, heavy chloroform, heavy acetonitrile, heavy acetone, heavy benzene, heavy cyclohexane, heavy water, heavy dichlorobenzene, heavy diethyl ether, heavy Examples include dimethylformamide, deuterated dimethyl sulfoxide, deuterated dioxane, deuterated ethyl acetate, deuterated ethanol, deuterated methanol, deuterated nitrobenzene, dehydrated pyridine, deuterated tetrachloroethane, deuterated toluene, deuterated trifluoroacetic acid and the like.

ＮＭＲ試料管１０の長さは、通常、１４０〜２２０ｍｍである。   The length of the NMR sample tube 10 is usually 140 to 220 mm.

外管１１及び内管１２を構成する材料としては、ＮＭＲを測定する際に悪影響を及ぼさなければ、特に限定されないが、ガラス、ポリプロピレン、ポリエチレン、ポリエチレンテレフタレート、ポリエーテルエーテルケトン、ポリ塩化ビニル、ポリテトラフルオロエチレン等が挙げられる。   The material constituting the outer tube 11 and the inner tube 12 is not particularly limited as long as it does not adversely affect the NMR measurement, but glass, polypropylene, polyethylene, polyethylene terephthalate, polyether ether ketone, polyvinyl chloride, Tetrafluoroethylene etc. are mentioned.

外管１１の厚さは、通常、０．１〜０．４ｍｍである。   The thickness of the outer tube 11 is usually 0.1 to 0.4 mm.

内管１２の厚さは、通常、０．１〜０．４ｍｍである。   The thickness of the inner tube 12 is usually 0.1 to 0.4 mm.

内管１２の内径は、通常、１〜９．５ｍｍである。   The inner diameter of the inner tube 12 is usually 1 to 9.5 mm.

外管１１の内径と内管１２の外径の差は、通常、０．１〜８．２ｍｍである。   The difference between the inner diameter of the outer tube 11 and the outer diameter of the inner tube 12 is usually 0.1 to 8.2 mm.

標準物質１３としては、特に限定されないが、フェナジン、トリアジン、マレイン酸、３−トリメチルシリルプロピオン酸ナトリウム、ジメチルシラペンタンスルホン酸ナトリウム、５−フルオロウラシル、ベンゼントリカルボン酸、ヘキサメチルジシロキサン、ベンゾキノン、ギ酸、酢酸、酢酸ナトリウム、無水酢酸、アクリル酸、ジメチルスルホン、アセトン、アセチルアセトン、シクロヘキサノン、ジエチルエーテル、１，１−ジエトキシエタン、エチルビニルエーテル、フラン、テトラヒドロフラン、１，４−ジオキサン、ジヒドロピラン、メタノール、エタノール、イソブチルアルコール、ｔ−ブチルアルコール、エチレングリコール、２−クロロエタノール、酢酸エチル、酢酸ビニル、アクリル酸メチル、オルトギ酸メチル、アセトアミド、ジメチルホルムアミド、トリメトキシベンゼン、トリオキサン、１，４−ビス（トリメチルシリル）ベンゼン、１，４−ジニトロベンゼン、アントラセン、ベンジルベンゾエート、ビフェニル、ジメチルイソフタレート、ジメチルホルムアミド、ヘキサメチルシクロトリシロキサン、メテナミン、フォログルシノール、ｔ−ブタノール、テトラメチルピラジン、エタクリン酸、ジメチルフラン、クロロホルム、ベンゼン、ジメチルスルホキシド、水、アセトアルデヒド等の１ＨＮＭＲ及び１３ＣＮＭＲ用の標準物質；トリフルオロエタノール、トリフルオロ酢酸、フルオロベンゼン、ヘキサフルオロイソプロパノール等の１９ＦＮＭＲ用の標準物質、テトラメチルシラン、ジメチルシラペンタンスルホン酸ナトリウム、３−トリメチルシリルプロピオン酸ナトリウム、１，４−ビス（トリメチルシリル）ベンゼン、トリメチルシリルエタンスルホンアミド、トリメチルシリルメタノール、トリメチルシリルアミン等の２９ＳｉＮＭＲ用の標準物質；水等の１７ＯＮＭＲ用の標準物質；リン酸等の３１ＰＮＭＲ用の標準物質等が挙げられる。中でも、定量性を考慮すると、１ＨＮＭＲ用の標準物質は、マレイン酸、テトラメチルシラン、３−トリメチルシリルプロピオン酸、１，４−ジオキサン、１，４−ビス（トリメチルシリル）ベンゼン、ベンゼントリカルボン酸、ジメチルシラペンタンスルホン酸ナトリウム、トリアジン、フェナジン、リン酸、トリフルオロ酢酸、水、ベンゼン、クロロホルム、メタノール又はジメチルスルホキシドが好ましい。 The standard substance 13 is not particularly limited, but phenazine, triazine, maleic acid, sodium 3-trimethylsilylpropionate, sodium dimethylsilapentanesulfonate, 5-fluorouracil, benzenetricarboxylic acid, hexamethyldisiloxane, benzoquinone, formic acid, acetic acid , Sodium acetate, acetic anhydride, acrylic acid, dimethylsulfone, acetone, acetylacetone, cyclohexanone, diethyl ether, 1,1-diethoxyethane, ethyl vinyl ether, furan, tetrahydrofuran, 1,4-dioxane, dihydropyran, methanol, ethanol, Isobutyl alcohol, t-butyl alcohol, ethylene glycol, 2-chloroethanol, ethyl acetate, vinyl acetate, methyl acrylate, methyl orthoformate, Toamide, dimethylformamide, trimethoxybenzene, trioxane, 1,4-bis (trimethylsilyl) benzene, 1,4-dinitrobenzene, anthracene, benzylbenzoate, biphenyl, dimethylisophthalate, dimethylformamide, hexamethylcyclotrisiloxane, methenamine, Standard substances for 1 HNMR and 13 CNMR such as fologlucinol, t-butanol, tetramethylpyrazine, ethacrynic acid, dimethylfuran, chloroform, benzene, dimethylsulfoxide, water, acetaldehyde; trifluoroethanol, trifluoroacetic acid, fluorobenzene , standard for 19 FNMR such hexafluoroisopropanol, tetramethylsilane, sodium dimethylsilanylbis pentanoic acid, 3-Doo Standard for 17 ONMR such as water; sodium methyl silyl propionic acid, 1,4-bis (trimethylsilyl) benzene, trimethylsilyl ethanesulfonamide, trimethylsilyl methanol, standards for 29 Si NMR, such as trimethylsilyl amine such as phosphoric acid 31 Examples include standard materials for PNMR. Among these, taking quantitativeness into consideration, the standard substances for 1 HNMR are maleic acid, tetramethylsilane, 3-trimethylsilylpropionic acid, 1,4-dioxane, 1,4-bis (trimethylsilyl) benzene, benzenetricarboxylic acid, dimethyl Preference is given to sodium silapentanesulfonate, triazine, phenazine, phosphoric acid, trifluoroacetic acid, water, benzene, chloroform, methanol or dimethyl sulfoxide.

外管１１と内管１２の間に入れる標準物質１３の量は、ＮＭＲを測定する際に悪影響を及ぼさない範囲であれば、特に限定されない。   The amount of the standard substance 13 placed between the outer tube 11 and the inner tube 12 is not particularly limited as long as it does not adversely affect the NMR measurement.

なお、ＮＭＲ試料管１０は、一端を閉じた管に外部標準物質１３を入れた後、その中に、同軸になるように、一端を閉じた管を配置し、管と管の間を溶閉することにより、製造することができる。内管１２の上部を外管１１に接するまで均等に広げて溶閉すると、定量性が向上する。   In the NMR sample tube 10, after putting the external standard substance 13 into a tube with one end closed, a tube with one end closed is arranged in the tube so as to be coaxial, and the tube is fused between the tubes. By doing so, it can be manufactured. If the upper part of the inner pipe 12 is spread evenly until it comes into contact with the outer pipe 11, the quantitative property is improved.

次に、１ＨＮＭＲを測定することにより、試料を定量分析する方法について説明する。 Next, a method for quantitative analysis of a sample by measuring 1 HNMR will be described.

まず、ＮＭＲ試料管１０のファクターを求める。具体的には、純度が既知のファクター用標準物質を重溶媒に溶解させたものを所定量内管１２に入れ、脱着可能な栓をした後、１ＨＮＭＲを測定する。このとき、内管１２に入れたファクター用標準物質の濃度をＡ０［ｍｏｌ／Ｌ］、１ＨＮＭＲスペクトルにおける標準物質１３の面積を１としたときのファクター用標準物質の１Ｈ分の面積をＢ０とすると、Ｆ［ｍｏｌ／Ｌ］は、式
Ｆ＝Ａ０／Ｂ０・・・（１）
で表される。 First, the factor of the NMR sample tube 10 is obtained. Specifically, a predetermined amount of a standard substance for factor having a known purity dissolved in a heavy solvent is put into a predetermined amount of the inner tube 12 and a demountable stopper is inserted, and then 1 HNMR is measured. At this time, the concentration of the standard substance for factor in the inner tube 12 is A 0 [mol / L], and the area of the standard substance 13 in the 1 HNMR spectrum is 1, and the area for 1H of the standard substance for factor is B Assuming 0 , F [mol / L] has the formula F = A 0 / B 0 (1)
It is represented by

ファクター用標準物質としては、特に限定されないが、フタル酸水素カリウム、エタノール、リン酸、トリフルオロ酢酸、ジメチルシラペンタンスルホン酸ナトリウム、３−トリメチルシリルプロピオン酸ナトリウム、水等が挙げられる。   The factor reference material is not particularly limited, and examples thereof include potassium hydrogen phthalate, ethanol, phosphoric acid, trifluoroacetic acid, sodium dimethylsilapentanesulfonate, sodium 3-trimethylsilylpropionate, and water.

なお、１ＨＮＭＲの定量性を考慮すると、Ｆを求める際に用いる標準物質１３の１ＨＮＭＲスペクトルのピークが、ファクター用標準物質の１ＨＮＭＲスペクトルのピークと重ならず、Ｆを求める際に用いるファクター用標準物質のピークが、標準物質１３の１ＨＮＭＲスペクトルのピークと重ならないことが好ましい。 In consideration of the quantitative of 1 HNMR, peak of 1 HNMR spectrum of the reference material 13 used to obtain the F is not overlap with the peak of the 1 HNMR spectrum of Factor for the standard substance, used to obtain the F-factor It is preferable that the peak of the standard material for use does not overlap with the peak of the 1 HNMR spectrum of the standard material 13.

次に、試料中の化合物Ｘ（分子量Ｍ）の含有量を求める。具体的には、試料を重溶媒に溶解させたものを所定量内管１２に入れ、脱着可能な栓をした後、１ＨＮＭＲを測定する。なお、試料が液体である場合は、重溶媒に溶解させずに、そのまま用いることもできる。このとき、内管１２に入れた試料の濃度をＡ１［ｇ／Ｌ］、１ＨＮＭＲスペクトルにおける標準物質１３の面積を１としたときの化合物Ｘの１Ｈ分の面積をＢ１とすると、内管１２に入れられた化合物Ｘの濃度Ｃ１［ｇ／Ｌ］は、式
Ｃ１＝Ｂ１×Ｆ×Ｍ・・・（２）
で表される。したがって、試料中の化合物Ｘの含有量Ｄ１［質量％］は、
Ｄ１＝（Ｃ１／Ａ１）×１００・・・（３）
で表される。

Next, the content of compound X (molecular weight M) in the sample is determined. Specifically, a sample in which a sample is dissolved in a heavy solvent is put into a predetermined amount of the inner tube 12 and a detachable stopper is inserted, and then 1 HNMR is measured. In addition, when a sample is a liquid, it can also be used as it is, without dissolving in a heavy solvent. At this time, if the concentration of the sample placed in the inner tube 12 is A 1 [g / L], and the area of the standard substance 13 in the 1 HNMR spectrum is 1, the area of 1H of the compound X is B 1 . The concentration C 1 [g / L] of the compound X put in the tube 12 is expressed by the formula C 1 = B 1 × F × M (2)
It is represented by Therefore, the content D 1 [% by mass] of the compound X in the sample is
D 1 = (C 1 / A 1 ) × 100 (3)
It is represented by

なお、１ＨＮＭＲの定量性を考慮すると、Ｄ１を求める際に用いる標準物質１３の１ＨＮＭＲスペクトルのピークが、試料のＮＭＲスペクトルのピークと重ならず、Ｄ１を求める際に用いる化合物Ｘの１ＨＮＭＲスペクトルのピークが、標準物質１３及び試料に含まれる化合物Ｘ以外の成分のＮＭＲスペクトルのピークと重ならないことが好ましい。 Note that one considering the quantitative of HNMR, the peak of the 1 HNMR spectrum of the reference material 13 used to obtain the D 1 is not overlap with the peak of the NMR spectrum of the sample, the compound X used to obtain the D 1 It is preferable that the peak of the 1 HNMR spectrum does not overlap with the peak of the NMR spectrum of components other than the standard substance 13 and the compound X contained in the sample.

また、試料に含まれる化合物Ｘ以外の成分の量も同時に求めてもよい。   Moreover, you may obtain | require the quantity of components other than the compound X contained in a sample simultaneously.

［ファクター用標準物質溶液の調製］
フタル酸水素カリウム（分子量２０４．２２１２）２００．２ｍｇを精密に量り、重水に溶解させ、正確に２０ｍＬとし、０．０４９０１５ｍｏｌ／Ｌのファクター用標準物質溶液を得た。 [Preparation of standard solution for factor]
200.2 mg of potassium hydrogen phthalate (molecular weight 204.2212) was precisely weighed and dissolved in heavy water to make exactly 20 mL, and a 0.049015 mol / L standard solution for factor was obtained.

［ファクターの評価］
外管１１と内管１２の間に、重水に溶解した標準物質１３（マレイン酸）が入れられたＮＭＲ試料管１０（図１参照）の内管１２にファクター用標準物質溶液を適量入れ、脱着可能な栓をした。次に、ＥＣＡ−４００（日本電子社製；４００ＭＨｚ）を用いて、パルス幅５．３５マイクロ秒、繰り返し時間約６０秒間、積算回数１６回の条件で、１ＨＮＭＲを３回測定した。得られた１ＨＮＭＲスペクトルからＢ０を得た（表１参照）。 [Evaluation of factors]
An appropriate amount of the standard solution for factor is put in the inner tube 12 of the NMR sample tube 10 (see FIG. 1) in which the standard material 13 (maleic acid) dissolved in heavy water is placed between the outer tube 11 and the inner tube 12, and desorption is performed. I plugged in. Next, 1 HNMR was measured three times using ECA-400 (manufactured by JEOL Ltd .; 400 MHz) under the conditions of a pulse width of 5.35 microseconds, a repetition time of about 60 seconds, and an integration count of 16 times. B 0 was obtained from the obtained 1 HNMR spectrum (see Table 1).

Figure 0005027891
次に、式（１）を用いて、ファクターＦを算出したところ、０．２１６８１［ｍｏｌ／Ｌ］となった。
Figure 0005027891
 Next, when the factor F was calculated using Formula (1), it was 0.21681 [mol / L].

［消毒液中のエタノールの濃度の評価］
ファクターを評価したＮＭＲ試料管１０の内管１２に消毒液を適量入れ、脱着可能な栓をした。次に、ファクターの評価と同一の条件で、１ＨＮＭＲを３回測定した。得られた１ＨＮＭＲスペクトル（図２参照）のエタノールのメチル基由来のピーク及びメチレン基由来のピークからＢ１を得た（表２参照）。 [Evaluation of ethanol concentration in disinfectant]
An appropriate amount of an antiseptic solution was placed in the inner tube 12 of the NMR sample tube 10 whose factor was evaluated, and a removable plug was inserted. Next, 1 HNMR was measured three times under the same conditions as the factor evaluation. B 1 was obtained from the methyl group-derived peak and the methylene group-derived peak of ethanol in the obtained 1 HNMR spectrum (see FIG. 2) (see Table 2).

Figure 0005027891
次に、式（２）を用いて、内管１２に入れられたエタノール（分子量４６．０７）の濃度Ｃ１を算出したところ、２４３．２３［ｇ／Ｌ］となった。
Figure 0005027891
 Next, when the concentration C 1 of ethanol (molecular weight 46.07) put in the inner tube 12 was calculated using the formula (2), it was 243.23 [g / L].

１０ ＮＭＲ試料管
１１ 外管
１２ 内管
１３ 標準物質 10 NMR sample tube 11 Outer tube 12 Inner tube 13 Standard substance

Claims (3)

二重管構造を有し、一端が閉じている第一の管の中に一端が閉じている第二の管が入れられている状態で、該第一の管と該第二の管の間が溶閉されており、該溶閉されている第一の管と第二の管の間に、定量用標準物質が入れられているＮＭＲ試料管にファクター用標準物質が重溶媒中に溶解している溶液を入れる工程と、
該ファクター用標準物質が重溶媒中に溶解している溶液が入れられたＮＭＲ試料管を用いて、前記ファクター用標準物質の１ＨＮＭＲスペクトルを測定することにより、ＮＭＲ試料管のファクターを求める工程と、
該ファクターが求められたＮＭＲ試料管に化合物Ｘを含む試料を入れる工程と、
該試料が入れられたＮＭＲ試料管を用いて、前記試料の １ ＨＮＭＲスペクトルを測定することにより、前記試料中の前記化合物Ｘの含有量を定量分析する工程を有し、
前記ファクター用標準物質が重溶媒中に溶解している溶液中の前記ファクター用標準物質の濃度をＡ０［ｍｏｌ／Ｌ］、前記ファクター用標準物質の１ＨＮＭＲスペクトルにおける前記定量用標準物質の面積を１としたときの前記ファクター用標準物質の１Ｈ分の面積をＢ０、前記ＮＭＲ試料管のファクターをＦ［ｍｏｌ／Ｌ］、前記化合物Ｘの分子量をＭ、前記ＮＭＲ試料管に入れられた試料の濃度をＡ １ ［ｇ／Ｌ］、前記試料の １ ＨＮＭＲスペクトルにおける前記定量用標準物質の面積を１としたときの前記化合物Ｘの１Ｈ分の面積をＢ １ 、前記ＮＭＲ試料管に入れられた化合物Ｘの濃度をＣ １ ［ｇ／Ｌ］、前記試料中の前記化合物Ｘの含有量をＤ １ ［質量％］とすると、式
Ｆ＝Ａ０／Ｂ０
Ｃ １ ＝Ｂ １ ×Ｆ×Ｍ
Ｄ １ ＝（Ｃ １ ／Ａ １ ）×１００
を満たすことを特徴とする分析方法。 A double tube structure with a second tube closed at one end in a first tube closed at one end, between the first tube and the second tube There are溶閉, between the first tube and the second tube being closed solution, factor reference material for the NMR sample tube quantitative standards are placed is dissolved in the heavy solvent A step of adding a solution,
Determining a factor of the NMR sample tube by measuring a 1 HNMR spectrum of the standard material for factor using an NMR sample tube containing a solution in which the standard material for factor is dissolved in a heavy solvent ; ,
Placing a sample containing Compound X in an NMR sample tube for which the factor was determined;
A step of quantitatively analyzing the content of the compound X in the sample by measuring a 1 HNMR spectrum of the sample using an NMR sample tube containing the sample;
The concentration of the standard substance for factor in the solution in which the standard substance for factor is dissolved in a heavy solvent is A 0 [mol / L], and the area of the standard substance for quantification in the 1 HNMR spectrum of the standard substance for factor The area of 1H of the standard material for factor when B is 1 , the factor of the NMR sample tube is F [mol / L] , the molecular weight of the compound X is M, and the NMR sample tube is placed in the NMR sample tube When the concentration of the sample is A 1 [g / L] and the area of the standard substance for quantification in the 1 HNMR spectrum of the sample is 1 , the area for 1H of the compound X is B 1 and put in the NMR sample tube. When the concentration of the obtained compound X is C 1 [g / L] and the content of the compound X in the sample is D 1 [mass%] , the formula F = A 0 / B 0
C 1 = B 1 × F × M
D 1 = (C 1 / A 1 ) × 100
An analysis method characterized by satisfying 前記定量用標準物質は、マレイン酸、テトラメチルシラン、３−トリメチルシリルプロピオン酸、１，４−ジオキサン、１，４−ビス（トリメチルシリル）ベンゼン、ベンゼントリカルボン酸、ジメチルシラペンタンスルホン酸ナトリウム、トリアジン、フェナジン、リン酸、トリフルオロ酢酸、水、ベンゼン、クロロホルム、メタノール又はジメチルスルホキシドであることを特徴とする請求項１に記載の分析方法。   The standard substances for quantification are maleic acid, tetramethylsilane, 3-trimethylsilylpropionic acid, 1,4-dioxane, 1,4-bis (trimethylsilyl) benzene, benzenetricarboxylic acid, sodium dimethylsilapentanesulfonate, triazine, phenazine The analysis method according to claim 1, which is phosphoric acid, trifluoroacetic acid, water, benzene, chloroform, methanol, or dimethyl sulfoxide. 前記ファクター用標準物質は、フタル酸水素カリウム、エタノール、リン酸、トリフルオロ酢酸、ジメチルシラペンタンスルホン酸ナトリウム、３−トリメチルシリルプロピオン酸ナトリウム又は水であることを特徴とする請求項１又は２に記載の分析方法。   The factor reference material is potassium hydrogen phthalate, ethanol, phosphoric acid, trifluoroacetic acid, sodium dimethylsilaptansulfonate, sodium 3-trimethylsilylpropionate, or water, according to claim 1 or 2. Analysis method.
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